E importante t che il chirurgo conosca il profilo molecolare del carcinoma del colon?

Transcription

1 E importante t che il chirurgo conosca il profilo molecolare del carcinoma del colon? Giuseppe Aprile Dipartimento di Oncologia Dipartimento di Oncologia Azienda Ospedaliero-Universitaria - Udine

2 Dr. Giuseppe Aprile In ottemperanza alla normativa ECM ed al principio di trasparenza delle fonti di finanziamento e dei rapporti con soggetti portatori di interessi commerciali in campo sanitario, si informano i discenti che negli ultimi due anni si sono avuti i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario: Rl Relatore a convegni/board scientifici: ifi i Roche, Merck, Amgen, Eli Lilly, Bayer, Sanofi

3 Metastatic colon cancer: Surgery MATTERS KOPETZ S, ET AL.J CLIN ONCOL 2009

4 MDT: no longer words only, but a REAL NEED Adam et al. The Oncologist 12

5 Why the MDT? Greater accuracy of disease staging Fewer treatment and referral delays Individualized evidence-based practice for patients Continuity of care Enhanced QoL Better clinical and survival outcome Adam et al, The Oncologist 12

6 Communication helps to understand each other Palliative Therapy Systemic/regional therapy for patients with never resectable dosease in an attempt to improve survival and quality of life. Neoadjuvant Therapy Preoperative systemic therapy for resectable hepatic metastases. Adjuvant Therapy Systemic/regional therapy post hepatic resection. Conversion Therapy Systemic/regional therapy utilized for patients with unresectable hepatic mets in an attempt to make the metastases resectable.

7 Defining resectability over time BEFORE 2006: by what is to be removed AFTER 2006: by what will remain Vauthey JN et al. AHPBA Consensus Conference, San Francisco, 2006

8 Techniques in surgery evolve continuously Wedge Resections No need for 1 cm margin Surgery + RFA Trans-metastases hepatectomy Two-stage hepatectomies (+/- PVE) ALPPS (liver partition) Repeat resections Resection of extrahepatic disease Elderly

9 Sopravvissuto o sopravvivente? Robert Zemeckis, Cast away 2000

10 sopravviventi sopravvissuti De Jong, et al. Ann Surg 2011

11 MCRC: patterns of recurrence after R patients treated with surgery for colorectal liver metastasis 57% patients recurred (median RFS time of 16.3 months) Intrahepatic only 43% Intra + extrahepatic 57% de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi institutional analysis of 1669 patients. Ann Surg

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13 Bittoni A et al, Crit Rev Oncol Hematol 2013

14 Marginally resectable Bittoni A et al, Crit Rev Oncol Hematol 2013

15 Control arm surgery alone pooled analysis of FCCD and ENG studies 60% relapse in 2 yrs adapted from Mitry et al. JCO 09

16 EORTC (EPOC study) design SURGERY 364 resectable CRC patients R FOLFOX x6 SURGERY FOLFOX O x6 364 patients t randomized d Potentially resectable ( 4 liver metastases) Goal: Improve PFS Interim objective: Evaluate tumor response to perioperative CT Perioperative CT (n = 182) 159 (87.3%) underwent surgery 151 (83.0%) resected Surgery (n=182) 170 (93.4%) underwent surgery 152 (83.0%) resected adapted from Mitry et al. JCO 09

17 Original PFS in the eligible population (2008) Nordlinger et al. Lancet 2008

18 Updated PFS (2013) Periop CT, mpfs: 20.0 mos Surgery Only, mpfs: mos HR:0.81 [ ] Nordlinger et al. Lancet Oncol 2013

19 Updated OS (2013) Periop CT, mos 61.3 mos Surgery Only, mpos: 54.3 mos HR:0.88 [ ] Nordlinger et al. Lancet Oncol 2013

20 New EPOC randomized phase III trial Primrose R, et al. ASCO 13

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23 More responses, more resections, more survival. Is the old paradigm still valid or it may now be challenged?

24 The old Folprecht s paradigm modified from Folprecht G et al, Ann Oncol 2005

25 Has been confirmed with time Jones R et al, Eur J Cancer 2014

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27 Fong s classics have turned old

28 How may we improve outcome results?

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30 MEDICO M, ET AL. NAT COMMUN 2015

31 Dinicolantonio F, ESMO 2014

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34 FAKIH MG. J CLIN ONCOL 2015

35 VAUTHEY JN, ET AL. ANN SURG 2013

36 HR 1.9 HR 2 VAUTHEY JN, ET AL. ANN SURG 2013

37 HR 2 VAUTHEY JN, ET AL. ANN SURG 2013

38 KEMENY NE, ET AL. CANCER 2014

39 KEMENY NE, ET AL. CANCER 2014

40 KEMENY NE, ET AL. CANCER 2014

41 KEMENY NE, ET AL. CANCER 2014

42 YAEGER R, ET AL. CANCER 2014

43 YAEGER R, ET AL. CANCER 2014

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46 KARAGKOUNIS G, ET AL. CANCER 2013

47 KARAGKOUNIS G, ET AL. CANCER 2013

48 KARAGKOUNIS G, ET AL. CANCER 2013

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52 BRAF MUTANT Do all you can to stop it immediately

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61 Personal conclusions Both medical oncologist and surgeons should be aware of RAS and BRAF status Should any resectable RAS mutant CRC patient be offered salvage surgery? Probably yes, but revise Fong s criteria, and be aware of the increased risk of lung, bone and brain mets. Should any resectable BRAF mutant CRC patient be offered salvage surgery? Not sure anymore. Consider V600E prognosis and disease biology.

62 E importante t che il chirurgo conosca il profilo molecolare del carcinoma del colon? Giuseppe Aprile Dipartimento di Oncologia Dipartimento di Oncologia Azienda Ospedaliero-Universitaria - Udine